Influence of location of acceleration sensor on physiological tremor of upper limb.

The physiological tremor of the upper limb in three positions of pronation, neutrality, and supination due to the movement of forearm was measured on four locations at the tip of the finger, the root of the finger in the hand, the wrist, and the elbow with use of an accelerated sensor. The evaluation of the total power, which was the summation of the power spectrum in the frequency range from 1 to 50 Hz, showed no significant difference in any of the positions. The maintenance of the upper limb at the horizontal level showed the coordination of the central nervous system due to the body parts of the upper arm, forearm, hand, and finger connected by the joint. The coherence spectra showed clear activation of the joint of the wrist in the main peak frequency of around 2.5 and 12.5 Hz in their respective positions. The value of the correlation coefficient in the location between the hand and finger was the largest at over 0.8, and those of the locations which connected the joint of the wrist between the forearm and hand and between the forearm and finger were significantly large with a value from 0.6 to 0.8. The mean time (i.e., arrival time) of the transmission from the proximal side (i.e., upper arm and forearm) to the distal side (i.e., hand and finger) in the upper limb was evaluated quantitatively to be 20 ms for pronation and supination, but the value was small for neutrality.

High plasma concentrations of osteopontin in patients with interstitial pneumonia.

Osteopontin (OPN) produced by alveolar macrophages functions as a fibrogenic cytokine in the development of bleomycin (BLM)-induced murine pulmonary fibrosis, and OPN mRNA is expressed on lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The present study investigates plasma OPN levels in human interstitial pneumonia (IP) and their relationships with disease severity by analyzing the correlation between plasma OPN concentrations and pulmonary functions. The concentrations of OPN in plasma were measured in 17 patients with IP, in 9 with sarcoidosis and in 20 healthy controls using an antigen-capture enzyme-linked immunosorbent assay. The concentrations of OPN in plasma were significantly higher in IP patients than in those with sarcoidosis or in controls. Based on a Receiver Operating Characteristic curve analysis, cut-off points between 300 and 380 ng/ml discriminated between IP and control subjects with 100% sensitivity and 100% specificity. In such case, the sensitivity for sarcoidosis decreased (55.5-33.3%) in cut-offs with 100% specificity. Plasma OPN levels inversely and closely correlated with arterial oxygen tension (PaO2) in patients with IP. Immunohistochemically, OPN was localized predominantly in macrophages and airway epithelium. These findings suggest that plasma OPN levels were found to be associated with the presence of IP, and that OPN play an important role in the development of IP.

Cortical potentials associated with voluntary, reflex, and spontaneous blinks as bilateral simultaneous eyelid movement.

Movement-related cortical potentials (MRCPs) associated with the contraction of m. orbicularis oculi related to three types of blinks (voluntary, reflex, and spontaneous) were measured for 12 normal subjects. The purpose of the present study was to estimate the role of the cerebral cortex in close association with the blinks caused by bilateral simultaneous eyelid movements. MRCPs were recorded by surface electrodes placed over the frontal to the parietal regions. The mean amplitude and the duration of the MRCPs for the three types of blinks were evaluated by an averaging technique for each subject. MRCPs for the voluntary blinks were evoked in all subjects. For the reflex and the spontaneous blinks, however, a clear negative rising deflection from the baseline was not obtained. The maximum amplitude of the MRCPs for the voluntary blinks was localized at the vertex region, though there was no significant difference between the durations of the MRCPs for the vertex region and for the other regions. Moreover, the positive potential following the voluntary and the spontaneous blinks was recognized in the parietal region. These results suggest that only the voluntary blinks are caused by the neural activation of the supplementary motor area (SMA), and in addition, the neural activation related to visual recognition is considered to be elicited by the voluntary and the spontaneous blinks.

Production of long-chain polyunsaturated fatty acids by monoxenic growth of labyrinthulids on oil-dispersed agar medium.

A novel method is proposed for the production of long-chain polyunsaturated fatty acids (LCPUFA) by labyrinthulids. The method comprises a monoxenic culture with Psychlobacter phenylpyruvicus, using agar medium in which oil was dispersed. Soybean oil (SBO) was selected as the optimum material for an oil-dispersed agar medium. The labyrinthulids showed three-dimensional growth and an anastomosing ectoplasmic network in the SBO-dispersed agar medium. The oil plate changed from an opaque culture to a more transparent culture, due to growth of the labyrinthulids. The optimum culture conditions were 25-30 degrees C, an initial pH of 6-10 and artificial seawater with a salt concentration of 50-100%. These conditions are close to those where these strains were isolated. The maximum LCPUFA production (0.59 g/l) and dry cell weight (4.93 g/l) was obtained using strain S3-2 (isolated from Ishigaki Island) with 1.5% SBO at 14 days. This value was about 30 times more than that using glucose instead of SBO. The method proposed is promising in terms of the production of LCPUFA from reproducible oils.

On the evaluation of muscle fiber conduction velocity considering waveform properties of an electromyogram in M. biceps brachii during voluntary isometric contraction.

The surface myoelectric signal during 20% maximum voluntary contraction was measured in m. biceps brachii using array electrodes for ten subjects in order to evaluate the distribution of muscle fiber conduction velocity (MFCV) in a whole muscle. MFCV was estimated by two calculating methods of the peak maximum method and the cross-correlation method from the myoelectric signals which were processed by techniques of the averaging and the non-averaging. It was found that the values of MFCV depended on the location irrespective of the kind of calculating method used and the kind of processing technique of myoelectric signal. In both the motor end-plate zone and the tendon zone, the values of MFCV showed more than 7.0 m/s. In the regions other than the motor end-plate zone and the tendon zone, the values of MFCV showed about 3.90 m/s which were almost constant. The statistical differences of the values of MFCV were in the same locations measured not recognized between the two calculating methods nor between the two processing techniques. In the cross-correlation method, the relation between MFCV and the electrode location was evaluated by both the maximum correlation coefficient and the amplitude ratio between the different neighboring channels to evaluate the conductive waveform properties of action potentials. The changes of parameters (i.e., MFCV, maximum correlation coefficient and amplitude ratio) depended on the electrode location. The values of MFCV significantly increased in the regions of the motor end-plate zone and the tendon zone, where the maximum correlation coefficient and amplitude ratio significantly decreased. The values of the coefficient of variance (CV) of three parameters in those regions were larger than those in other regions, i.e., the regions other than the motor end-plate zone and the tendon zone. A high maximum correlation coefficient and a high amplitude ratio were necessary for a reliable measurement of the MFCV.

Influence of hyperbaric environment on physiological tremor.

The effect of pressured environment from 1 to 24 ATA (Atmosphere Absolute) on total power spectrum (TP) of physiological tremor, whose value was the sum of power spectra for frequency range in 0.5-50 Hz, was investigated. The main effects obtained were as follows. (1) In the case of 3 ATA, TP during the pressure holding period denoted a similar value as the value in 1 ATA. In the latter half of the period, the TP increased. When the pressured environment is 4 ATA, in which the partial pressure of the nitrogen gas was 3.6 ATA, the TP decreased during the pressure holding period compared with the value in 1 ATA. Nitrogen narcosis was recognized at the partial pressure of 3.6 ATA, thus the effect denoted a decrease of TP. (2) In the cases of 16 and 19 ATA using heliox gas, during the pressure holding period, TP decreased compared with the value in 1 ATA, but in the case of 24 ATA the value increased. The partial pressure of helium gas of 23.6 ATA indicated a high pressure nervous syndrome, therefore, the influence of high pressure on TP was recognized as one of the causes of the increase of TP. (3) The influence of inhibitors of the autonomic nervous system on TP during the pressure holding period of 3 ATA was recognized. After intake of the inhibitor for the parasympathetic nerve (atropine) during the pressure period, TP increased, while for the intake of the inhibitor for the sympathetic nerve (propanol), TP decreased.

Hypertrophic pulmonary osteoarthropathy associated with non-small cell lung cancer demonstrated growth hormone-releasing hormone by immunohistochemical analysis.

Hypertrophic pulmonary osteoarthropathy (HPO) associated with non-small cell lung cancer in a 58-year-old man was accompanied by an elevated serum level of growth hormone (GH). HPO rapidly disappeared after resection of the primary tumor and the elevation of serum GH was resolved. Immunohistochemically the tumor contained growth hormone-releasing hormone (GHRH) but not GH. These findings suggest that the high serum GH level due to ectopic GHRH production in the tumor, was a contributing factor in HPO. This is the second reported case of non-small cell lung cancer which was immunohistochemically positive for GHRH associated with HPO.

Prednisolone inhibits an IgE-mediated late-phase allergic cutaneous reactionby interfering with the activation of mast cells in mice.

Epicutaneous antigen challenge in passively sensitized mice with IgE produces a biphasic cutaneous response which peaks 1 h (immediate-phase reaction) and 24 h (late-phase reaction; LPR) after the antigen challenge. In this model, anaphylactic degranulation and interleukin 6 (IL-6) expression between 4 and 8 h are observed in resident mast cells as the preceding stage of LPR. Prednisolone at a dose of 3 mg kg(-1) clearly inhibited the LPR when administered 2 h before and 4 h after antigen challenge. Slight or no inhibition of LPR was observed by prednisolone administered 6-12 h after challenge. Histologically, prednisolone treatment 2 h before antigen challenge completely inhibited edema and inflammatory cell infiltration, while treatment at 6 h did not at all. In order to investigate the relationship between inhibition of LPR by prednisolone and mast cell activation, the effects of prednisolone on degranulation of mast cells and IL-6 expression in mast cells were investigated. 8 h after antigen challenge, prednisolone clearly inhibited the increase in the number of anaphylactic degranulated and IL-6-positive mast cells by administration 2 h before challenge, but did not affect it by administration 6 h after challenge. These data indicate that the inhibitory mechanism of prednisolone on LPR, at least, involves the inhibition of mast cell activation before LPR.

Distribution of muscle fiber conduction velocity of m. masseter during voluntary isometric contraction.

Muscle fiber conduction velocity (MFCV) is the velocity of an interference wave due to muscle fiber action potentials. In general, it has been reported that the value of MFCV in m. masseter is larger than that in limb and trunk muscles. But the values of MFCV in the reports were measured in part of the muscle, and the distribution of MFCV in the whole muscle including the end-plate and the tendon has not been measured. In this study, surface myoelectric signals are recorded in m. masseter during voluntary isometric contractions of 20, 30, and 40% MVC (maximum voluntary contraction) in eleven healthy male subjects with the use of array electrodes. The value of MFCV is found directly using an averaging method. The end-plate zone is concentrated in the lower quarter of the muscle. The distribution of MFCV depends on the location of the measured electrode. The largest value of MFCV of more than 20.0 m/s is obtained in the locations of the end-plate and the tendon. The minimum value of MFCV is obtained at the location of 10 mm measured from the end-plate along the direction of the muscle fiber to the tendon of the upper side. The mean values with the standard deviations during 20, 30, and 40% MVC are 10.3 +/- 0.7, 11.6 +/- 0.7, and 12.2 +/- 0.8 m/s, respectively. The MFCVs between the different neighboring locations are compared and found to be significant by a level of 1% for each contraction level. The MFCVs increase depending on the contraction levels for various electrode locations on the muscle.

[Primary pulmonary cryptococcosis with endobronchial lesion].

A 19-year old man was admitted to our hospital with fever and productive cough. Chest X-ray films revealed multiple nodular shadows accompanied by a fusing tendency in the right middle field. A diagnosis of bacterial pneumonia was indicated, and the patient was treated with antibiotics. However, because this failed to resolve the nodular shadows, bronchofibroscopy was performed. Examination with a fiberoptic bronchoscope revealed an elevated lesion in the truncus intermedius. Histopathologic examination of a specimen obtained by transbronchial biopsy revealed cryptococcal organisms with the infiltration of monocytes. These findings yielded a diagnosis of pulmonary cryptococcosis with endobronchial lesion. After 6 months of treatment with fluconazole, the multiple nodular shadows disappeared. Comparison of bronchoscopic findings before and after fluconazole treatment clearly demonstrated the efficacy of the therapy.

Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice.

BACKGROUND: In mice that are passively sensitized to IgE, cutaneous antigen challenge produces a biphasic response with peaks at 1 and 24 hours after challenge. OBJECTIVE: We investigated the role of mast cells in the IgE-mediated late-phase reaction in mice. METHODS: We histologically and ultrastructurally investigated the morphologic changes of mast cells during the biphasic responses. RESULTS: Degranulation of mast cells, which was observed between 4 and 24 hours after challenge, reached a peak at 8 hours. Piecemeal degranulation was seen during the immediate phase reaction. The number of IL-6-positive mast cells was increased after 4 hours in both IgE-sensitized and unsensitized mice, but positive cells showed a greater increase in sensitized mice and reached a peak after 8 hours. With in situ hybridization experiments, mast cells were positive for IL-6 messenger RNA at 6 hours after challenge. CONCLUSION: These findings indicate that anaphylactic degranulation of mast cells and the expression of IL-6 mRNA within 4 hours after antigen challenge are important for the onset of the late-phase allergic cutaneous reaction in mice.

Muscle fiber conduction velocity during isometric contraction and the recovery period.

Changes of muscle fiber conduction velocity (MFCV) detected by surface array electrodes during an isometric contraction and the recovery period were evaluated. The location on skin measured for action potentials of muscle fiber in m. biceps brachii was a distance of 5 mm and 30 mm from the end-plate to the distal tendon. The MFCV was evaluated by averaging raw EMG waves. The MFCVs at both locations declined gradually during the loads of sustained isometric contractions of 30, 50, and 70% of the maximum voluntary contraction (MVC). The degree of the decrease of the MFCV was extremely intense during a sustained contraction of 70% MVC. The values of the MFCV at the location of 5 mm from the end-plate in the period close to the exhaustion state showed a significant decrease compared with the values in the initial period during the contractions for the above three kinds of loads, while the decrease of the MFCV at the location of 30 mm from the end-plate was not found to be so significant during the contractions. In the recovery period, the contraction of 5% MVC was maintained, and the resultant MFCVs restored gradually to the value of the initial period. At the location of 5 mm from the end-plate, the MFCVs at 15 minutes after the end of the load were significantly higher than those just after the end of the load. At the location of 30 mm from the end-plate, the increases of the MFCVs during the recovery period did not show significant changes. Changes of the MFCV during the isometric contraction and the recovery period depend greatly on the location of the electrodes measured for the action potentials of the muscle fibers.

[A small cell lung cancer shadow resembling beads on chest radiographs].

We present a case of small cell lung cancer whose shadow resembles bead son chest radiographs. An 81-year-old woman who had been receiving treatment from her doctor for pulmonary emphysema and chronic respiratory failure consulted our department because a small nodular shadow had been detected radiographically in the right lower lung field. The bead-like shadows in the radiographs and tomograms extended from the periphery of the right lower lobe to the pulmonary hilum. This case of small cell lung cancer appeared in chest radiographs to have an unusual shape.

[A case of pulmonary manifestation associated with myelodysplastic syndrome].

A 69-year-old woman with myelodysplastic syndrome (MDS) was admitted to our hospital because of recurrent fever and pulmonary infiltration shadows. On the seventh day of hospitalization, she had an attack of high fever and cough and laboratory tests revealed an elevated leukocyte count and elevated serum C-reactive protein. Chest radiographs showed infiltration shadows in the right middle and lower lung fields. Because a diagnosis of bacterial pneumonia was initially suggested, she was treated with antibiotics. However, the infiltration shadows on the chest radiograph had not improve, so bronchofiberscopy was performed. Analysis of fluid obtained by bronchoalveolar lavage (BAL) showed an increase in the total cell count, predominantly in lymphocytes and neutrophils. A transbronchial biopsy specimen showed infiltration of numerous neutrophils with necrosis under the bronchial epithelium, and edematous septa were infiltrated with numerous neutrophils and lymphocytes. BAL, blood, urine, bone marrow, and sputum cultures were all free of bacteria, mycobacteria and fungi. Interstitial infiltration by numbers of neutrophils associated with MDS was diagnosed and steroid treatment was performed.

A needle-type immunotherapeutic system incorporating laser light and platonin in combination with ethanol injection in the treatment of cancer growing in deep organs.

Platonin is a potent cell-activating agent and a photosensitizing dye characterized by a typical absorption peak at 590 nm. It has been already clarified that macrophage activity is enhanced synergistically by platonin administration together with laser light irradiation. This method is considered to be useful in cancer immunotherapy. In this study, a needle-type therapeutic system incorporating this method was applied for the therapy of a homogeneous tumor grafted onto mice. The tumor was strongly cicatrized by collagen fibers at an early stage of the treatment. A high T/B cell ratio of lymphocytes was observed in the peripheral blood of the treated mice. In addition, a high survival ratio was seen, especially in the group of concomitant therapy with ethanol injection (PEI method). It was determined that the induction of high immunopotentiation of mice was triggered by ethanol injection at an early stage. These results demonstrated that the system is reliable for the treatment of cancer in deep organs such as a liver, requiring no major surgical intervention.

Phase I study of cisplatin and docetaxel plus mitomycin C in patients with metastatic non-small cell lung cancer.

BACKGROUND: Docetaxel, cisplatin and mitomycin C are some of the active drugs used in the treatment of patients with metastatic non-small cell lung cancer (NSCLC). The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose of the three drugs in combination for such patients. METHODS: Chemotherapy-native patients with metastatic NSCLC were enrolled in this study. The doses of docetaxel and cisplatin were fixed at 60 and 80 mg/m2, respectively. It was planned to increase the dose of mitomycin C from 4 to 6 and 8 mg/m2. All drugs were administered on day 1 and repeated every 3-4 weeks. RESULTS: All six patients received 60 mg/m2 of docetaxel and 80 mg/m2 of cisplatin, three of them with 4 mg/m2 of mitomycin C (level 1) and the other three with 6 mg/m2 of mitomycin C (level 2). Two of the three level 2 patients experienced dose-limiting toxicities (DLTs) in first cycle: febrile neutropenia and grade 3 hyponatremia. Based on these data, the MTD was concluded to be 60 mg/m2 for docetaxel, 80 mg/m2 for cisplatin and 6 mg/m2 for mitomycin C. Evaluation of the data from all of the cycles, however, showed that four of the six patients experienced DLTs. CONCLUSIONS: The addition of mitomycin C to docetaxel and cisplatin resulted in relatively high toxicities. It was impossible to use a high enough dose of mitomycin C to improve the survival of NSCLC patients. We therefore concluded that further evaluation of this combination is unwarranted.

Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis.

Artepillin C was extracted from Brazilian propolis. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) has a molecular weight of 300.40 and possesses antibacterial activity. When artepillin C was applied to human and murine malignant tumor cells in vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth of tumor cells was clearly inhibited. The artepillin C was found to cause significant damage to solid tumor and leukemic cells by the MTT assay, DNA synthesis assay, and morphological observation in vitro. When xenografts of human tumor cells were transplanted into nude mice, the cytotoxic effects of artepillin C were most noticeable in carcinoma and malignant melanoma. Apoptosis, abortive mitosis, and massive necrosis combined were identified by histological observation after intratumor injection of 500 microg of artepillin C three times a week. In addition to suppression of tumor growth, there was an increase in the ratio of CD4/CD8 T cells, and in the total number of helper T cells. These findings indicate that artepillin C activates the immune system, and possesses direct antitumor activity.

Expression of exon 5 deleted estrogen receptor variant messenger RNA in human uterine myometrium and leiomyoma.

To examine the relationship between uterine leiomyoma, an estrogen-dependent tumor and its estrogen receptor, the relative amounts of wild type estrogen receptor (WT) mRNA and exon 5 deleted estrogen receptor variant (D5-ER) mRNA to G3PDH mRNA were examined in human uterine myometrium and leiomyoma specimens obtained from 46 patients in 3 age groups (group A: 41-45 years old, group B: 46-50 years old, group C: 51-54 years old) using a quantitative reverse transcription polymerase chain reaction method (RT-PCR). D5-ER mRNA was co-expressed with WT mRNA in all myometrium and leiomyoma specimens. In myometrium, the relative amount of WT decreased with aging, but in leiomyoma, it was high in group B. The relative amount of D5-ER mRNA and the ratio of D5-ER mRNA to WT mRNA (D5/WT ratio) were significantly higher in group C in both myometrium and leiomyoma. The percentage of the patients whose D5/WT ratio was higher in leiomyoma than in myometrium (L/M ratio>1.0) increased with age. These findings suggest that D5-ER increases to supplement the decreasine in WT in uterine tissues toward menopause and that D5-ER plays a more active role in leiomyoma than in myometrium during the perimenopausal period.

A needle type therapeutic system incorporating laser light and lumin for immunotherapy of cancer growing in deep organs.

Lumin is a potent cell-activating agent and a photosensitizer characterized by absorption peaks at 670 nm and 770 nm. It has already been demonstrated that macrophase activity is enhanced greatly by lumin administration with laser light irradiation and that this method is useful in cancer immunotherapy. In this study, a new needle type therapeutic system was developed for the immunotherapy of cancer growing in deep human organs. A human lung cancer grafted onto nude mice was strongly cicatrized by collagen fibres about four weeks after the first treatment. The collagen fibres seemed to seal-off the tumor and prevent its growth with intense cicatrization. In addition, a high T/B cell ratio of lymphocytes was observed in the peripheral blood of the treated mice, although the thymus is congenitally absent from nude mice. These results demonstrated that the system is a reliable method for cancer treatment in deep organs without side effects and/or major surgical intervention.

Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides derived from hemoglobin.

From proteolytic digest of swine hemoglobin, we isolated four peptide, E-1 (Phe-Gln-Lys-Val-Val-Ala), E-2 (Phe-Gln-Lys-Val-Val-Ala-Gly), peptide 30-3 (Phe-Gln-Lys-Val-Val-Ala-Lys) and H-1 (Gly-Lys-Lys-Val-Leu-Gln). These peptides inhibited angiotensin I-converting enzyme activity with an IC50 of 5.8, 7.4, 2.1 and 1.9 microM, respectively. Oral administration of 50 mg/kg E-1 and 50 mg/kg H-1 decreased blood pressure in spontaneously hypertensive rats. In normotensive rats, oral administration of 500 mg/kg E-1 and 500 mg/kg H-1 inhibited the pressor effect of i.v. administrated 300 ng/kg angiotensin I, possibly by inhibiting its conversion to angiotensin II. These results suggest that these peptides are orally effective inhibitors of angiotensin I-converting enzyme that have a hypotensive effect.